Student and Faculty Publications
Publication Date
3-20-2023
Journal
International Journal of Molecular Sciences
Abstract
The survival of malignant leukemic cells is dependent on DNA damage repair (DDR) signaling. Reverse Phase Protein Array (RPPA) data sets were assembled using diagnostic samples from 810 adult and 500 pediatric acute myelogenous leukemia (AML) patients and were probed with 412 and 296 strictly validated antibodies, respectively, including those detecting the expression of proteins directly involved in DDR. Unbiased hierarchical clustering identified strong recurrent DDR protein expression patterns in both adult and pediatric AML. Globally, DDR expression was associated with gene mutational statuses and was prognostic for outcomes including overall survival (OS), relapse rate, and remission duration (RD). In adult patients, seven DDR proteins were individually prognostic for either RD or OS. When DDR proteins were analyzed together with DDR-related proteins operating in diverse cellular signaling pathways, these expanded groupings were also highly prognostic for OS. Analysis of patients treated with either conventional chemotherapy or venetoclax combined with a hypomethylating agent revealed protein clusters that differentially predicted favorable from unfavorable prognoses within each therapy cohort. Collectively, this investigation provides insight into variable DDR pathway activation in AML and may help direct future individualized DDR-targeted therapies in AML patients.
Keywords
Humans, Adult, Child, Prognosis, Leukemia, Myeloid, Acute, DNA Repair, DNA Damage, Discoidin Domain Receptors, AML, proteomics, RPPA, DNA damage
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Hematology Commons, Medical Molecular Biology Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 36982970